A 12-year-old boy has persistent microscopic haematuria detected on school screening. He also has bilateral sensorineural hearing loss. His maternal uncle had kidney failure at age 30. Renal biopsy electron microscopy shows irregular thickening and thinning of the glomerular basement membrane with splitting and lamellation of the lamina densa. What is the underlying defect?

• A Mutation in the gene encoding podocin
• B Mutation in the gene encoding the alpha-5 chain of type IV collagen ✓
• C Defective laminin beta-2 leading to congenital nephrotic syndrome
• D Autoantibodies against the NC1 domain of the alpha-3 chain of type IV collagen

Explanation

The triad of hereditary haematuria, sensorineural deafness, and X-linked inheritance points to Alport syndrome, caused by mutations in COL4B5 encoding the alpha-5 chain of type IV collagen. The classic electron microscopy finding is splitting and lamellation of the lamina densa producing a basket-weave appearance. Option D describes anti-GBM antibodies seen in Goodpasture syndrome, while podocin mutations cause steroid-resistant focal segmental glomerulosclerosis.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.